Abstract / Project Summary Application of high-throughput gene expression technology to systemic sclerosis (SSc) skin biopsies, isolated SSc cell lines and peripheral blood cell (PBC) samples has shown that it will be an important tool for understanding the diversity in rheumatic diseases, as well as changes to the underlying gene expression pathways. The Translational Genomics and Data Integration (TGDI) core will use novel bioinformatic and genomic methods that have been developed and already successfully implemented in the core PI's laboratory to analyze SSc samples and healthy controls. High quality RNA will be prepared and analyzed by RNA-sequencing using protocols established in the PIs laboratory. All data are processed using standard and novel methods that use a combination of algorithms that test for differential gene expression, enriched pathways analysis and put the changes into the context of the all publicly available SSc high- throughput data. The TGDI core provides network analyses using a Scleroderma Specific Network (SSN) to analyze data from cells lines, mouse models, clinical trials, and single cell RNA-seq (scRNA-seq), thus providing a measure of how well a therapy eliminates the aberrant gene expression we observe in SSc. The goals of this core are to 1) Provide high quality RNA-seq analyses for individual projects and process the resulting data in a rigorously controlled analysis pipeline to provide differential gene expression and patient subset assignments, 2) provide a systems biology and network analysis of gene expression data in SSc using our novel SSN, and 3) perform meta- analyses of SSc clinical trials using both existing data as well as new data generated as part of the CORT research projects. Relevance: High-throughput gene expression analysis has allowed the definition of subsets of SSc and identified deregulated pathways that can be targeted therapeutically. Recent studies have shown that a patient's subset or activated pathways at baseline can be predictive of clinical response. This core, provides high-throughput studies, data analyses for CORT investigators, bioinformatics and systems biology analyses of SSc samples.